Preparation, Optimization, and Evaluation of Dolutegravir Nanosuspension: In Vitro and In Vivo Characterization

Purpose In this study, a nanosuspension of dolutegravir, an antiviral drug with solubility issues, was developed and optimized using a Design of Experiments (DoE) approach. The nanosuspension showed a significant improvement in drug dissolution compared to the pure drug.Methods The formulation process involved high-speed homogenization and probe sonication techniques, with Soluplus as the selected surfactant. The optimized nanosuspension demonstrated desirable pharmacokinetic profiles, surface morphology, and drug content. In vitro and in vivo studies confirmed the enhanced performance of the nanosuspension.Results The dolutegravir nanoparticles had a mean size of 337.1 nm, a low polydispersity index, and a negative zeta potential, indicating good stability. Experimental results in Wistar rats showed higher bioavailability for the nanosuspension compared to the pure drug, as evidenced by the increased AUC value. The optimized formulation exhibited improved in vitro drug release, increased solubility, and good stability. The sonication time played a crucial role in controlling the nanoparticle size. Further characterization using differential scanning calorimetry and X-ray diffraction confirmed the amorphous nature of the drug in the nanosuspension, explaining the enhanced solubility.Conclusion In conclusion, the nanosuspension approach offers a promising solution for improving the bioavailability of poorly soluble drugs like dolutegravir. The developed DGSD-Nanosuspension formulation shows potential for effectively treating HIV-positive individuals by enhancing drug absorption and therapeutic efficacy. This innovative approach holds promise for overcoming solubility challenges in HIV medication and may contribute to better treatment outcomes. Further research and clinical studies are needed to validate the effectiveness and safety of DGSD-Nanosuspension as a viable delivery system for dolutegravir and other poorly soluble drugs.